85% of sporadic hyperparathyroidism has a solitary adenoma with a surgical cure rate of 90-95%. The remainder of cases have multiple tumors. Of these, about 90% achieve a long remission at initial operation. Adverse outcomes are increased in multigland disease and in cases with prior failed operation; the adverse outcomes include hypoparathyroidism, persistence, and late recurrence. Approximately half of new referrals to NIH have had prior failed neck exploration for hyperparathyroidism; they have been referred because of our expertise for these cases. The surgical success rate at NIH in these difficult cases has been 95%. This group is enriched for multigland hyperparathyroidism and thus for hereditary causes. Efforts are continuing to improve the methods for preoperative tumor localization in this challenging group. Prior failure also increases the likelihood that no normal parathyroid tissue remains. Thus cryopreservation and fresh or cryopreserved autografts have been developed to decrease the likelihood of permanent hypoparathyroidism. This program represented the first endocrine tumor imaging program at NIH in the 1960s and continues as a world-wide standard for endocrine tumor imaging.